title: Pharmacokinetic interactions of maraviroc with darunavir-ritonavir, etravirine, and etravirine-darunavir-ritonavir in healthy volunteers: results of two drug interaction trials.
abstract: The effects of darunavir-ritonavir at 600 and 100 mg twice daily (b.i.d.) alone, 200 mg of etravirine b.i.d. alone, or 600 and 100 mg of darunavir-ritonavir b.i.d. with 200 mg etravirine b.i.d. at steady state on the steady-state pharmacokinetics of maraviroc, and vice versa, in healthy volunteers were investigated in two phase I, randomized, two-period crossover studies. Safety and tolerability were also assessed. Coadministration of 150 mg maraviroc b.i.d. with darunavir-ritonavir increased the area under the plasma concentration-time curve from 0 to 12 h (AUC12) for maraviroc 4.05-fold relative to 150 mg of maraviroc b.i.d. alone. Coadministration of 300 mg maraviroc b.i.d. with etravirine decreased the maraviroc AUC12 by 53% relative to 300 mg maraviroc b.i.d. alone. Coadministration of 150 mg maraviroc b.i.d. with etravirine-darunavir-ritonavir increased the maraviroc AUC12 3.10-fold relative to 150 mg maraviroc b.i.d. alone. Maraviroc did not significantly affect the pharmacokinetics of etravirine, darunavir, or ritonavir. Short-term coadministration of maraviroc with darunavir-ritonavir, etravirine, or both was generally well tolerated, with no safety issues reported in either trial. Maraviroc can be coadministered with darunavir-ritonavir, etravirine, or etravirine-darunavir-ritonavir. Maraviroc should be dosed at 600 mg b.i.d. with etravirine in the absence of a potent inhibitor of cytochrome P450 3A (CYP3A) (i.e., a boosted protease inhibitor) or at 150 mg b.i.d. when coadministered with darunavir-ritonavir with or without etravirine.
authors.affiliation: Tibotec, Inc., 1125 Trenton-Harbourton Rd., K20605, Titusville, NJ 08560, USA. tkakuda@its.jnj.com
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Kakuda
authors.forename: Samantha
authors.initials: S
authors.lastname: Abel
authors.forename: John
authors.initials: J
authors.lastname: Davis
authors.forename: Julia
authors.initials: J
authors.lastname: Hamlin
authors.forename: Monika
authors.initials: M
authors.lastname: Schöller-Gyüre
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mack
authors.forename: Noella
authors.initials: N
authors.lastname: Ndongo
authors.forename: Wendy
authors.initials: W
authors.lastname: Petit
authors.forename: Caroline
authors.initials: C
authors.lastname: Ridgway
authors.forename: Vanitha
authors.initials: V
authors.lastname: Sekar
authors.forename: Sarah
authors.initials: S
authors.lastname: Tweedy
authors.forename: Richard M W
authors.initials: RM
authors.lastname: Hoetelmans
mesh_terms: D000293:Adolescent; D000328:Adult; D003510:Cyclohexanes / Q000009:adverse effects / Q000493:pharmacokinetics*; D000069454:Darunavir; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D009570:Nitriles; D011724:Pyridazines / Q000009:adverse effects / Q000493:pharmacokinetics*; D011743:Pyrimidines; D019438:Ritonavir / Q000009:adverse effects / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000009:adverse effects / Q000493:pharmacokinetics*; D014230:Triazoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D003510:Cyclohexanes; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D013449:Sulfonamides; D014230:Triazoles; C451734:etravirine; D000077592:Maraviroc; D019438:Ritonavir; D000069454:Darunavir